The American Heart Association (AHA) has issued recommendations for interventions to reduce the risk of cardiovascular complications in patients with diabetes mellitus. Developed by the AHA Science Advisory and Coordinating Committee, the AHA scientific statement appears in the September 7, 1999 issue of Circulation. It is also available on the Circulation Web site (http://www.circulationaha.org). In addition, single reprints may be obtained by calling 800-242-8721 or writing the American Heart Association, Public Information, 7272 Greenville Ave., Dallas, TX 75231-4596. The following summarizes the recommendations for reducing the risk of cardiovascular disease and its complications in patients who have diabetes.

Predisposing Risk Factors for Cardiovascular Disease

The AHA scientific statement begins with the assertion that “from the point of view of cardiovascular medicine, it may be appropriate to say ‘diabetes is a cardiovascular disease.’” The report notes that the combination of insulin resistance, dyslipidemia, hypertension and prothrombotic factors often precedes the development of type 2 diabetes (formerly known as non–insulin-dependent diabetes) by many years. This constellation is referred to in the report as the metabolic syndrome.

According to the AHA report, myocardial ischemia from coronary atherosclerosis frequently is asymptomatic in patients with diabetes. As a result, atherosclerosis has often progressed to involve multiple vessels before ischemic symptoms occur and before treatment is initiated. In addition, the poor prognosis in patients with diabetes and ischemic heart disease seems to relate to an enhanced myocardial dysfunction that leads to accelerated heart failure. Factors that probably underlie diabetic cardiomyopathy include severe coronary atherosclerosis, prolonged hypertension, chronic hyperglycemia, microvascular disease, glycosylation of myocardial proteins and autonomic neuropathy. Diabetic cardiomyopathy may be prevented or forestalled by good glycemic control, better control of hypertension and the use of cholesterol-lowering agents to prevent atherosclerosis. In addition, prevention or treatment of obesity and promotion of physical activity are advocated as important measures for preventing cardiovascular disease and diabetes.

Insulin Resistance and the Metabolic Syndrome

According to the report, studies suggest that insulin resistance is a multisystem disorder that induces multiple metabolic alterations. Metabolic risk factors that commonly occur in patients with insulin resistance are atherogenic dyslipidemia, hypertension, glucose intolerance and a prothrombotic state. The dyslipidemia is characterized by an elevated very-low-density lipoprotein level, small low-density lipoprotein (LDL) particles and a low high-density lipoprotein (HDL) level. Coagulation alterations that predispose the patient to arterial thrombosis include an increased fibrinogen level, increased plasminogen activator inhibitor-1 and various platelet abnormalities.

Risk Assessment and Clinical Evaluation

The report states that the first step in reducing the risk of cardiovascular disease in patients with diabetes is identification of risk factors such as cigarette smoking, hypertension, abnormal serum lipid levels, excess body weight and abdominal obesity, physical inactivity and a family history of cardiovascular disease.

Early detection of cardiovascular disease may reduce morbidity and mortality in patients with diabetes. Detection of subclinical disease requires a careful assessment for evidence of claudication, angina, dyspnea on exertion and cerebrovascular disease. Carotid and femoral arteries should be assessed for bruits and peripheral pulses should be evaluated. The ratio of ankle-to-brachial artery systolic blood pressure may serve as a marker for peripheral vascular disease. The urine should be checked for microalbuminuria. Electrocardiographic evidence of left ventricular hypertrophy is a strong predictor of morbidity and mortality from coronary heart disease.

Special considerations for exercise stress testing include the blunted blood pressure and heart rate responses that are often present in patients with diabetes. In addition, painless ST-segment depression is common in these patients, and the diagnostic specificity of ST-segment depression is often reduced in patients with diabetes because of a previous silent myocardial infarction, conduction abnormalities and increased left ventricular mass. An alternative to exercise testing is perfusion scintigraphy. Although not recommended routinely, ambulatory electrocardiographic monitoring may be useful for detecting silent ischemia.

The report notes that autonomic dysfunction is associated with a 50 percent mortality rate at five years. Periodic evaluation should include an assessment for evidence of autonomic dysfunction. Autonomic dysfunction increases the risk of general anesthesia and complications following elective surgery. Autonomic dysfunction may be present if two or more of the following abnormalities are found on examination: a resting heart rate (supine) of 100 beats per minute, an excessive diastolic blood pressure response to hand-grip exercise, an abnormal expiratory/inspiratory RR-interval ratio and postural hypotension.

Table 1 outlines important points for evaluating and monitoring the patient's renal status. Aggressive management of hypertension, to blood pressure levels of less than 130/85 mm Hg, is recommended as a measure to prevent the development of end-stage renal disease.

Primary Prevention

The AHA statement notes that type 2 diabetes can be viewed as the end product of years of metabolic stress accompanying insulin resistance. As the report states, “the clock starts ticking for acceleration of atherogenesis long before the onset of hyperglycemia.” Early detection of risk factors associated with the metabolic syndrome is needed to institute primary prevention measures in patients at risk of diabetes. Evidence of insulin resistance includes the presence of abdominal obesity or borderline abdominal obesity, high-normal blood pressure or mild hypertension, high-normal triglycerides (150 to 250 mg per dL [1.70 to 2.82 mmol per L]), reduced HDL cholesterol (less than 40 mg per dL [1.05 mmol per L] in men and less than 50 mg per dL [1.30 mmol per L] in women) and borderline high-risk LDL cholesterol (130 to 159 mg per dL [3.35 to 4.10 mmol per L]). In some patients, impaired fasting glucose (110 to 126 mg per dL [6.10 to 7.00 mmol per L]) may be present. Impaired fasting glucose usually signifies longstanding insulin resistance and is a strong risk factor for type 2 diabetes. The report states that early implementation of primary measures for prevention of cardiovascular disease will probably delay the onset of type 2 diabetes as well as reduce the risk of cardiovascular disease.

Interventions for Risk Reduction in Cardiovascular Disease

According to the AHA statement, clinical trials show that comprehensive medical intervention in patients with diabetes and atherosclerotic cardiovascular disease can have a considerable impact. It can extend the overall rate of survival, improve quality of life, decrease the need for intervention procedures such as angioplasty and coronary artery bypass surgery, and reduce the incidence of subsequent myocardial infarction. Table 2 on page 567 summarizes the recommendations for interventions to reduce the risk in patients with diabetes and evidence of cardiovascular disease.